<i>LRP1B</i> mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma

Cao, Can-hui; Liu, Rang; Lin, Xin-ran; Luo, Jia-qi; Cao, Li-juan; Zhang, Qiu-ju; Lin, Shou-ren; Geng, Lan; Sun, Zhong-yi; Ye, Si-kang; Yu, Zhi-ying; Shi, Yu; Xia, Xi

doi:10.7150/ijbs.56970

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Int J Biol Sci 2021; 17(7):1744-1756. doi:10.7150/ijbs.56970 This issue Cite

Research Paper

LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma

Can-hui Cao¹, Rang Liu¹, Xin-ran Lin¹, Jia-qi Luo¹, Li-juan Cao¹, Qiu-ju Zhang¹, Shou-ren Lin¹, Lan Geng¹, Zhong-yi Sun¹, Si-kang Ye², Zhi-ying Yu^3✉, Yu Shi^1✉, Xi Xia^1✉

1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong, 518036, China.
2. Department of Critical Care Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
3. Department of Gynecology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.

Citation:

Cao Ch, Liu R, Lin Xr, Luo Jq, Cao Lj, Zhang Qj, Lin Sr, Geng L, Sun Zy, Ye Sk, Yu Zy, Shi Y, Xia X. LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma. Int J Biol Sci 2021; 17(7):1744-1756. doi:10.7150/ijbs.56970. https://www.ijbs.com/v17p1744.htm

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Abstract

Human papillomavirus (HPV) infection and gene mutations were reputed as key factors in cervical carcinoma (CC) and head and neck squamous cell carcinoma (HNSCC). However, the associations of HPV status and gene mutations remain to be determined. This study aims to identify molecular patterns of LRP1B mutation and HPV status via rewiring tumor samples of HNSCC (n=1478) and CC (n=178) from the TCGA dataset. Here, we found that LRP1B mutation was associated with HPV status in CC (P=0.040) and HNSCC (P=0.044), especially in HPV 16 integrated CC (P=0.036). Cancer survival analysis demonstrated that samples with LRP1B mutation showed poor disease outcomes in CC (P=0.013) and HNSCC (P=0.0124). In addition, the expression status of LPR1B was more favorable for prediction than TP53 or RB1 in CC and HNSCC. Mutation clustering analysis showed that samples with LRP1B mutation showed higher mutation count in CC (P=1.76e-67) and HNSCC (P<10e-10). Further analysis identified 289 co-occurrence genes in these two cancer types, which were enriched in PI3K signaling, cell division process, and chromosome segregation process, et al. The 289-co-occurrence gene signature identified a cluster of patients with a higher portion of copy number variation (CNV) lost in the genome, different tumor HPV status (P<10e-10), higher mutation count (P<10e-10), higher fraction genome altered value (P=2.078e-4), higher aneuploidy score (P=3.362e-4), and earlier started the smoking year (P=2.572e-4), which were associated with shorter overall survival (P=0.0103) in CC and HNSCC samples. Overall, LRP1B mutation was associated with tumor HPV status and was an unfavorable prognostic biomarker for CC and HNSCC.

Keywords: LRP1B mutation, tumor HPV status, cervical carcinoma, head and neck squamous cell carcinoma, tumor mutation count

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APA

Cao, C.h., Liu, R., Lin, X.r., Luo, J.q., Cao, L.j., Zhang, Q.j., Lin, S.r., Geng, L., Sun, Z.y., Ye, S.k., Yu, Z.y., Shi, Y., Xia, X. (2021). LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma. International Journal of Biological Sciences, 17(7), 1744-1756. https://doi.org/10.7150/ijbs.56970.

ACS

Cao, C.h.; Liu, R.; Lin, X.r.; Luo, J.q.; Cao, L.j.; Zhang, Q.j.; Lin, S.r.; Geng, L.; Sun, Z.y.; Ye, S.k.; Yu, Z.y.; Shi, Y.; Xia, X. LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma. Int. J. Biol. Sci. 2021, 17 (7), 1744-1756. DOI: 10.7150/ijbs.56970.

NLM

CSE

Cao Ch, Liu R, Lin Xr, Luo Jq, Cao Lj, Zhang Qj, Lin Sr, Geng L, Sun Zy, Ye Sk, Yu Zy, Shi Y, Xia X. 2021. LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma. Int J Biol Sci. 17(7):1744-1756.

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